Menopause and aging: Changes in the immune system—A review

Background

The higher risk of women developing autoimmune diseases suggests that immune system is mediated by sex steroids.

Objective

To review the effects of aging and menopause in immune system.

Methods

A systematic review of in vitro, animal and human studies involving aging and menopause and immune system was carried out. An electronic search based on Internet search engines, MEDLINE (1966–June 2010) and the Cochrane Controlled Clinical Trials Register was done.

Results

After crossing-cleaning the reference lists, a total of 688 studies dealing with immune system and menopause were identified. Of them, 30 were considered selectable. The concept of immunosenescence reflects changes in both cellular and serological immune responses throughout the process of generating specific response to foreign antigens. This may be related with a higher incidence of infectious and chronic diseases. After menopause, there is an increase in pro-inflammatory serum markers (IL1, IL6, TNF-alpha), an increase in response of the immune blood cells to these cytokines, a decrease in CD4 T and B lymphocytes and a decrease in the cytotoxic activity of NK cells. Additionally, IL-6 is a key factor in bone resorption and also seems to be associated with other diseases more common after menopause such as diabetes, atherosclerosis and cardiovascular disease.

Conclusions

Most of the studies suggested that in addition to age, in postmenopausal women, changes of the immune system have been attributed to estrogen deprivation. Furthermore, recent studies point out changes in immune response related to use or cessation of hormone replacement at menopause.     

Menopause and the central nervous system: intervention options

The central nervous system is an important target for sex steroid hormones. During the climateric period the rapid decline of gonadal steroids causes neuroendocrine changes in different areas of the brain. The failure of gonadal hormone production brings specific symptoms due to the central nervous system derangement. At the hypotalamic level estrogen withdrawal gives rise to vasomotor symptoms, eating behavior disorders and altered blood pressure control. Psychological disturbances such as depression, anxiety, irritability and mood fluctuation are related to estrogen-induced changes in the lymbic system. The hypothesis of specific neuroanatomical and neurophysiological effects of estrogen on the brain may also explain the correlation between estrogen deficiency and cognitive disturbances such as Alzheimer's type dementia (AD). The increasing interest in the influence of sex steroids on brain function has focused attention on hormonal replacement therapy. Clinical and epidemiological studies have demonstrated that estrogen therapy exerts a positive effect on vasomotor instability and improves psychological disturbances. The positive effects of estrogen on mood are probably related to its stimulatory action on adrenergic and serotoninergic tone. Estrogen may influence the cognitive function through different biological actions. Estrogen administration increases total cerebral and cerebellar blood flow, cerebral glucose administration and improves cholinergic tone, a key neurotransmitter in learning and memory. The evidence suggests that hormone replacement therapy may reduce the relative risk of developing AD. Progestagens and androgen may also have a role in the control of mood disorders. At present, few data are available regarding the influence that selective estrogen receptor modulators, a new class of compounds, can exert on the brain.     

Menopause, oestrogens and arthritis

The menopause coincides with the appearance of many of the common arthritic conditions and with the lessening of severity of others such as SLE. The hormonal changes that occur may modulate these diseases. Thus, hormonal manipulation may have either beneficial or detrimental effects on the incidence and activity of a number of common joint diseases. We review the evidence regarding the effect of the menopause and oestrogen replacement therapy on the pathogenesis, incidence and prevalence and disease activity of osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus and carpal tunnel syndrome.     

他汀类药物对免疫细胞功能的调节作用及机制

他汀类药物是羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶的抑制剂,因其显著的降脂功能而广泛应用于治疗动脉粥样硬化和心血管疾病.近年来研究发现,他汀类药物在CD4+T细胞介导的多种自身免疫性疾病中显示了免疫调节功能,可有效预防和治疗这类疾病.本文将对他汀类药物的免疫调节功能及潜在机制进行初步的探讨.     

Menopause, the metabolic syndrome, and mind-body therapies

Cardiovascular disease risk rises sharply with menopause, likely due to the coincident increase in insulin resistance and related atherogenic changes that together comprise the metabolic or insulin resistance syndrome, a cluster of metabolic and hemodynamic abnormalities strongly implicated in the pathogenesis and progression of cardiovascular disease. A growing body of research suggests that traditional mind-body practices such as yoga, tai chi, and qigong may offer safe and cost-effective strategies for reducing insulin resistance syndrome-related risk factors for cardiovascular disease in older populations, including postmenopausal women. Current evidence suggests that these practices may reduce insulin resistance and related physiological risk factors for cardiovascular disease; improve mood, well-being, and sleep; decrease sympathetic activation; and enhance cardiovagal function. However, additional rigorous studies are needed to confirm existing findings and to examine long-term effects on cardiovascular health.     

Potential role of statins for the management of immune reconstitution syndrome

It has become evident that while a robust inflammatory response plays a critical role in eradicating invading microbes, dysregulated immunity can be detrimental to the host if an optimal balance between the inflammatory and anti-inflammatory reactions is disrupted. Opportunistic infection-associated immune reconstitution syndrome is characterized by an aggressive inflammatory immune response and its management remains challenging and largely unknown. Statins, in addition to their lipid lower effects have anti-inflammatory attributes and there is precedence for the use of these agents as a therapeutic modality for autoimmune inflammatory disorders which have similar underlying pathogenesis as immune reconstitution syndrome. We hypothesize that statins may have a potential role for the management of immune reconstitution syndrome. Our proposal has biologic and translational implications for optimizing outcomes in patients with immune reconstitution syndrome.     

Vitamin D,the immune system and asthma

The effects of vitamin-D on bone metabolism and calcium homeostasis have long been recognized. Emerging evidence has implicated vitamin-D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. Vitamin-D deficiency has been found to be associated with several immune-mediated diseases, susceptibility to infection and cancer. Recently, there has been increasing interest in the possible link between vitamin-D and asthma. Further elucidation of the role of vitamin-D in lung development and immune system function may hold profound implications for the prevention and treatment of asthma.     

Menopause and estrogen deficiency as a risk factor in dementing illness: hypothesis on the biological basis

The positive efficacy of estrogen replacement therapy (ERT) in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) is a matter of intense debate among clinicians and neuroscientists. The experimental and preliminary clinical evidence supporting the use of ERT are based on epidemiological data and on the study of the effect of estrogens on several aspects of brain homeostasis, including the modulation of neurotransmitters and vascular changes. In spite of numerous data available the mechanisms underlying the putative estrogen effects in neurodegenerative diseases are largely unknown. The aim of this paper is to discuss and elaborate on some of the hypotheses and controversial findings currently present in this field.     

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis

OBJECTIVES: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. METHODS: We studied 18 fertile middle-aged normotensive women (48 +/- 1.5 years, range 46-51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. RESULTS: Oophorectomy increased the mean values of 24 h (P < 0.001), daytime (P < 0.05), and nighttime (P < 0.01) diastolic blood pressure and nighttime systolic blood pressure (P < 0.01). Blood pressure increase was associated with a rise in forearm vascular resistance (P < 0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17beta-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. CONCLUSIONS: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.     

Red blood cells, hemoglobin and the immune system

The paramount function of the red blood cells (RBCs) is generally reckoned to be oxygen carriage. The possibility that they now participate in the defensive mechanism of the human body is ignored and neglected, despite the fact that the RBCs are both mechanical and biochemical barriers against infections, bacteria, and blood parasites. Immune reactions are regulated to ensure harmony between the red and white blood cell populations. This hypothesis will lead to better comprehension of blood cell functions in various physiological and pathological conditions.     

Wear particles, periprosthetic osteolysis and the immune system

The immune system modulates many key biological processes in humans. However, the exact role of the immune system in particle-associated periprosthetic osteolysis is controversial. Human tissue retrieval studies, in vivo and in vitro experiments suggest that the immune response to polymer particles is non-specific and macrophage-mediated. Lymphocytes may modulate this response. However direct lymphocyte activation by polymer particle-protein complexes seems unlikely. However, metallic byproducts may complex with serum proteins and lead to a Type IV, lymphocyte-mediated immune reaction. In predisposed individuals, this reaction may rarely lead to persistent painful joint effusions, necessitating debridement and excision of the bearing surfaces of the prosthesis. In these patients, retrieved periprosthetic tissues exhibit histological evidence of perivascular lymphocytic cuffing. These findings are worrisome, given the fact that increasing numbers of metal-on-metal joint implants are being implanted in younger more active individuals worldwide.     

Menopause, hormone replacement therapy and cancer

OBJECTIVE: To comparatively review available evidence on hormone replacement therapy (HRT) and cancer. METHODS: Qualitative literature review. RESULTS: Most potential favorable and adverse effects on cancer risk of HRT are restricted to current users. On the basis of observational epidemiological data, the RR of breast cancer is moderately elevated in current and recent HRT users, and increases by about 2.3% per year with longer duration of use, but the effect drops after cessation and largely, if not totally, disappears after about 5 years. Unopposed estrogen use is strongly related to endometrial cancer risk, but cyclic combined oestrogen-progestin treatment appears to largely or totally reduce this side effect, if progestin are used for at least 14 days per cycle. However, combined HRT may be associated with higher risk of breast cancer as compared to unopposed estrogens. HRT has been inversely related to colorectal cancer, although the issue of causal relation remains open to discussion. No consistent association was reported for ovarian, liver, other digestive or lung cancer. CONCLUSIONS: Recommendations for prolonged HRT use must be considered on an individual basis, taking into account the presence of other risk factors mainly for breast cancer, such as family history of breast cancer or a personal history of benign breast disease, as well as individual risk for other chronic diseases.     

Review: Free radicals, antioxidants, and the immune system

Oxygen-derived free radicals are important in both natural and acquired immunity. Neutrophil and macrophage phagocytosis stimulates various cellular processes including the "respiratory burst" whereby increased cellular oxygen uptake results in the production of the potent oxidant bactericidal agents, hypochlorous acid and hydroxyl radical. In addition, nitric oxide, a gaseous radical produced by macrophages, reacts with superoxide to form peroxynitrite, also a potent bactericidal agent. Conversely, oxidative stress may be detrimental in acquired immunity by activation of nuclear factor kappa B, which governs gene expression involving various cytokines, chemokines, and cell adhesion molecules, among others. However, antioxidant supplementation essentially reverses several age-associated immune deficiencies, resulting in increased levels of interleukin-2, elevated numbers of total lymphocytes and T-cell subsets, enhanced mitogen responsiveness, increased killer cell activity, augmented antibody response to antigen stimulation, decreased lipid peroxidation, and decreased prostaglandin synthesis.